Most neoplasias of the uterine cervix are associated with specific types of human papillomaviruses (HPV). The current concept is that invasive carcinoma are preceded by a long-standing stage of cervical intra-epithelial neoplasia (CIN), an heterogeneous group of disease classified as CIN1, CIN2, or CIN3 according to the severity of their histological abnormalities (Richart R. Obstetrics & Gynecology 1990;75:131–132).
CIN1 are the most frequent lesions, particularly in young women, and may follow different courses without treatment: a spontaneous regression occurs in 50–60% of patients whereas persistence or progression toward CIN2/3 is observed in the remaining cases (Östor A. International Journal of Gynecological Pathology 1993;12:186–192). The oncogenicity of associated-HPV type may influence the disease outcome (Schlecht N F, et al. J Natl Cancer Inst 2003;95(17):1336–43.), but little is known concerning the role of host-linked parameters, such as immunological factors, also likely to be implied in the natural history of these lesions.
Cellular-mediated immunity has been found to be involved in the host response against specific HPV types (Kadish A S, et al. J Natl Cancer Inst 1997;89(17):1285–93.) and may thus account, at least in part, for the regression of CIN. Experimental and clinical studies have also suggested that immunogenetic determinants related to HLA-class II genotype could play a part in tumour progression. In the model of tumours induced in rabbit by the Shope papillomavirus, the regression and malignant conversion of papillomas were found to be linked to the MHC class II genes (Han R, et al. Nature 1992;356:66–68.). In human, positive associations were reported between invasive cervical cancer and DQB1*301 (Madeleine M M, et al. J Infect Dis 2002;186(11):1565–74.; Wank R, Thomssen C. Nature 1991;352:723–725.), DQB1*1501 (Apple R J, et al. Nat Genet 1994;6(2):157–62.) or DQB1*1101 (Madeleine M M, et al. J Infect Dis 2002; Lin P, et al. Cancer Epidemiol Biomarkers Prev 2001;10(10):1037–45.) HLA class II alleles. However, no significant associations were found in other groups of patients (Glew S S, et al. Hum Immunol 1993;37(3):157–64.). In contrast, a negative association of the DRB1*13 allele with cervical cancer developed in patients from different geographic areas has been reported, namely Europe (Apple R J, et al. Journal of the National Cancer Institute 1995;87:427–435.; Sastre-Garau X, et al. Int J Cancer 1996;69(3):159–64.), Africa (Lin P, et al. Cancer Epidemiol Biomarkers Prev 2001;10(10):1037–45.) or North America (Madeleine M M, et al. J Infect Dis 2002;186(11):1565–74.). These data suggest that DRB1*13 alleles may be linked to a protective effect against HPV-associated lesion.
There is a strong need of objective biological criteria which would differentiate CIN corresponding to potential precursors of invasive cancer requiring immediate ablative therapy from those in which the treatment could be withheld for a while. The identification of such a criteria could allow a substantial benefit in terms of cost and morbidity in the care of high grade CIN, especially in young women.